Markevich2004_MAPK_phosphoRandomMM

  public model
Short description

The model corresponds to the schema 3 of Markevich et al 2004, as described in the figure 2 and the supplementary table S3, and modelled using Michaelis-Menten like kinetics. Phosphorylations follow distributive random kinetics, while dephosphorylations follow an ordered mechanism.

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2007 The BioModels Team.
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Format
SBML (L2V1)
Related Publication
  • Signaling switches and bistability arising from multisite phosphorylation in protein kinase cascades.
  • Markevich NI, Hoek JB, Kholodenko BN
  • The Journal of cell biology , 2/ 2004 , Volume 164 , pages: 353-359
  • Department of Pathology, Anatomy, and Cell Biology, Thomas Jefferson University, 1020 Locust St., Philadelphia, PA 19107, USA.
  • Mitogen-activated protein kinase (MAPK) cascades can operate as bistable switches residing in either of two different stable states. MAPK cascades are often embedded in positive feedback loops, which are considered to be a prerequisite for bistable behavior. Here we demonstrate that in the absence of any imposed feedback regulation, bistability and hysteresis can arise solely from a distributive kinetic mechanism of the two-site MAPK phosphorylation and dephosphorylation. Importantly, the reported kinetic properties of the kinase (MEK) and phosphatase (MKP3) of extracellular signal-regulated kinase (ERK) fulfill the essential requirements for generating a bistable switch at a single MAPK cascade level. Likewise, a cycle where multisite phosphorylations are performed by different kinases, but dephosphorylation reactions are catalyzed by the same phosphatase, can also exhibit bistability and hysteresis. Hence, bistability induced by multisite covalent modification may be a widespread mechanism of the control of protein activity.
Contributors
Nicolas Le Novère

Metadata information

is
BioModels Database MODEL6618620128
BioModels Database BIOMD0000000029
isDescribedBy
PubMed 14744999
hasTaxon
Taxonomy Xenopus laevis
isVersionOf
Gene Ontology GO:0000165
Curation status
Curated
  • Model originally submitted by : Nicolas Le Novère
  • Submitted: 13-Sep-2005 14:37:12
  • Last Modified: 15-May-2012 22:42:56
Revisions
  • Version: 2 public model Download this version
    • Submitted on: 15-May-2012 22:42:56
    • Submitted by: Nicolas Le Novère
    • With comment: Current version of Markevich2004_MAPK_phosphoRandomMM
  • Version: 1 public model Download this version
    • Submitted on: 13-Sep-2005 14:37:12
    • Submitted by: Nicolas Le Novère
    • With comment: Original import of Markevich2004_MAPK_phosphoRandomMM